INFLUENCE OF CALCIUM AND OTHER DIVALENT-CATIONS ON PROTEIN-TURNOVER IN RAT SKELETAL-MUSCLE
INFLUENCE OF CALCIUM AND OTHER DIVALENT-CATIONS ON PROTEIN-TURNOVER IN RAT SKELETAL-MUSCLE
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DOI：
10.1152/ajpendo.1986.250.6.e702
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发表时间：
1986-06-01
影响因子：
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通讯作者：
GOLDBERG, AL
中科院分区：
文献类型：
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作者：
BARACOS, V;GREENBERG, RE;GOLDBERG, AL
当大鼠肌肉在无钙培养液中孵育时，其蛋白质分解率显著低于完全培养液(2.58 mM Ca~(2+))。Dantrolene和3，4，5-三甲氧基苯甲酸8-(二乙氨基)辛酯是肌浆网钙释放的抑制剂，也降低了肌肉的蛋白分解。当加入钙离子(直到5.16 mM)时，完整的比目鱼肌和指长伸肌的蛋白水解率逐渐增加，最高可达70%，在切断的横隔肌中，蛋白水解率最高可达300%。添加Ca~(2+)对肌肉中的ATP或磷酸肌酸含量没有影响，对蛋白质合成略有增加或根本不影响。Sr2+、Ba2+和Mn2+也促进了蛋白质的降解，但效果不如Ca2+，而Mg2+则抑制了Ca2+对蛋白质的促进作用。钙离子的这种刺激作用不受电压依赖性钙通道、钙调蛋白、金属内切酶、微丝或微管形成或Mersalyl抑制剂的影响。高钙水平也增加了前列腺素(PG)E2的产生，尽管PGE2的增加似乎不是蛋白质分解增加所必需的。EP-475或亮肽素可阻止钙离子诱导的肌肉蛋白分解。相反，这些硫醇蛋白水解酶的抑制剂并不影响无钙介质中的蛋白质分解。因此，细胞外的钙离子激活，而镁离子抑制涉及硫醇蛋白水解酶的蛋白分解途径。
When rat muscles were incubated in Ca2+-free media, their rates of protein breakdown were significantly lower than in complete medium (2.58 mM Ca2+). Dantrolene and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, inhibitors of Ca2+ release from the sarcoplasmic reticulum, also reduced muscle proteolysis. When Ca2+ was added (up to 5.16 mM), proteolysis increased progressively up top 70% in the intact soleus and extensor digitorium longus muscles and up to 300% in the cut diaphragm preparation. Addition of Ca2+ did not affect the muscles'' ATP or phosphocreatine content and increased protein synthesis slightly or not at all. Sr2+, Ba2+ and Mn2+ also increased proteolysis, but were less effective than Ca2+, Mg2+ inhibited the enhancement of proteolysis by Ca2+. This stimulation by Ca2+ was not affected by inhibitors of voltage-dependent Ca2+ channels, calmodulin, metalloendoproteases, microfilament or microtubule formation, or mersalyl. High Ca2+ levels also increased prostaglandin (PG) E2 production, although a rise in PGE2 did not appear essential for the increased proteolysis. The proteolysis induced by Ca2+ was prevented in muscles treated with Ep-475 or leupeptin. By contrast, these inhibitors of thiol proteases did not affect protein breakdown in Ca2+-free medium. Thus extracellular Ca2+ activates and Mg2+ inhibits a proteolytic pathway involving thiol proteases.